Data collection for the study was completed in 1999 with over 1500 women enrolled. Fifty-seven percent of the random sample participants were African American and response rates (>80% of those screened) were similar for blacks and whites. Our first aim has been completed. Thirty-eight percent of the participants in the random sample arm had been previously diagnosed with fibroids. Of those with no prior diagnosis who had ultrasound examinations, a further 50% had fibroids. However, 13% of premenopausal women refused the study sonogram examination or missed their appointment, and 17% of participants were postmenopausal and not offered a study ultrasound. A subset of this latter group had fibroid status verified because we retrieved surgery and pathology records of their hysterectomies. David Dunson developed a method to combine data on prior diagnosis, the ultrasound data, and the medical record data to estimate the age-specific cumulative incidence of fibroids in an unbiased manner for black and white women. By their late 40s the cumulative incidence was over 80% in blacks and approaching 70% in whites. Blacks were at significantly higher risk at any given age (p<0.001) even after adjusting for parity and obesity. The data indicated that blacks were more likely to develop fibroids at younger ages and were more likely to have multiple fibroids. The size of the largest fibroid was very similar for blacks and whites who had been previously diagnosed with fibroids, but among women who had newly detected fibroids at the study sonogram, blacks had more fibroids >2cm in diameter. Fibroid size and tumor size are being used to extend the methods for estimating the age-specific cumulative incidence. The high cumulative incidence of fibroids in both ethnic groups strengthens the need to identify those women who are likely to have clinically relevant fibroids. Important factors probably include early onset and rapid tumor growth. These are features we are trying to address in our risk factor analysis and in designing further research. We are currently in the process of identifying risk factors, the second aim. We have data on tumor size for those with ultrasound data. Our analysis examines the relationship between hypothesized risk factors and fibroid size status. Survivorship analysis is used to identify factors related to age of diagnosis/detection. Potential risk factors are modeled as time-dependent variables. Hypotheses have been developed regarding age, parity/lactation, obesity, and infection. When the effects of these factors can be appropriately adjusted for, we will examine data on pesticides and other exposures. Addressing the third aim, three investigations are currently ongoing. (1) Gordon Flake, a human pathologist at NIEHS, is characterizing our entire sample of tumors histologically for proliferative characteristics, cellularity, degenerative changes, and identification of any particular pathological tumor types; to describe the variability among tumors and compare characteristics of the tumors from the same woman. (2) Darlene Dixon is comparing the expression of receptors and growth factors in tumor vs normal myometrium, currently is focusing on the role of IGF-I and its receptor in tumor growth. (3) Jane Schroeder is investigating the role of intracellular uterine infection in fibroid development by examining viral DNA in myometrial and fibroid tissues. In addition to the original aims, Anissa Vines has interviewed a large subset of the black women in the study (n=476) to measure perceived racism (conceptualized as a chronic stressor that could adversely affect health). She has validated her instrument, and is assessing the level of perceived racism and the women's emotional and behavioral responses to it. She also will investigate the relationship between racism and central obesity, as measured by waist to hip ratio. Jane Hoppin is exploring the possibility of measuring phthalates in The Fibroid Study participants, thus is comparing phthalate measurements in consecutive-day urine specimens collected from a subset of participants. If day-to-day variation is small, assay of a single specimen from each woman might provide a useful estimate of relative exposure levels, but large day-to-day variation precludes use of a one-time biomarker.